Chiral phospholane transition metal catalysts

ABSTRACT

Chiral 2,5-disubstituted phospholanes useful as transition metal ligands in asymmetric catalysis and processes for their preparation are disclosed.

This is a division of application Ser. No. 07/904,764, filed Jun. 26,1992, now U.S. Pat. No. 5,206,398 which in turn is a division ofapplication Ser. No. 07/644,526 filed Jan. 23, 1991, now U.S. Pat. No.5,177,338 which in turn is a division of application Ser. No. 07/524,737filed May 17, 1990 now U.S. Pat. No. 5,008,457.

FIELD OF THE INVENTION

The invention relates to novel chiral 2,5-disubstituted phospholanes anda method for their preparation. The compounds, when complexed withtransition metals, are efficient catalyst precursors for theenantioselective hydrogenation of unsaturated substrates.

BACKGROUND OF THE INVENTION

The development of novel catalytic systems exhibiting unique reactivityand high enantioselectivity requires the synthesis of chiral ligands fortransition metals. Generally, some of the most successful chiral ligandshave been chelating phosphines pocessing a C₂ symmetry axis. Thesynthesis of these phosphines in optically pure form often involvestedious synthetic routes that are limited to only one antipode orrequire a resolution step.

One synthetic route is through a diol intermediate. S. Masamune et al.,Journal of Organic Chemistry, Vol. 54, p. 1755 (1989) teaches use ofBaker's yeast for the reduction of 2,5-hexanedione to the corresponding(S,S)-diol, followed by reaction with methanesulfonyl chloride and ringclosure with benzylamine to form the optically pure(2R,5R)-2,5-dimethylpyrrolidine. Wilson et al., Synlett, pp. 199-200,April (1990) disclose similar use of a diol intermediate formed via aBaker's yeast reduction of a diketone in the preparation of a2,5-dimethylphospholane (Compound 10). The phospholane is prepared byreacting the diol with methanesulfonyl chloride followed byphenylphosphine in the presence of potassium hydroxide. However,enzymatic reductions generally provide only one enantiomer of thedesired product, and can have limitations such as high substratespecificity, low product yields, or involved isolation procedures.

In addition, many of the chiral phosphines known in the art have atleast two aryl substituents on the phosphorus, rendering that centerrelatively electron poor. The mechanism of asymmetric induction usingthese phosphines has been linked to the proper conformationalrelationship between the phenyl groups on the phosphorus centers.

More recently, chiral phosphines having relatively electron-richphosphorus centers have been reported. Brunner et al., Journal ofOrganometallic Chemistry, Vol. 328, PP. 71-80 (1987) teach3,4-disubstituted phospholanes derived from tartaric acid having chloro,methoxy, or dimethylamino substituents. These were complexed withmanganese and rhodium and used as catalysts in the hydrogenation ofalpha-N-acetamidocinnamic acid. Relatively low optical yields of(S)-N-acetylphenylalanine of from 6.6% enantiomeric excess to 16.8%enantiomeric excess were obtained.

A need exists for transition metal complexes providing high levels ofstereochemical control and asymmetric induction in stoichiometric andcatalytic transformations. A need also exists for efficient syntheticroutes for the preparation of chiral ligands having a high degree ofenantiomeric purity for transition metal catalysts.

It is therefore an object of the present invention to provide novelphospholane compounds as chiral ligands for transition metals.

It is a further object of the present invention to provide transitionmetal catalysts which provide high levels of stereochemical control ofreactions.

It is a further object of the present invention to provide transitionmetal catalysts which result in high levels of asymmetric induction inhydrogenation reactions.

It is a further object of the present invention to provide efficientsynthetic routes for the preparation of these phospholane compounds.

SUMMARY OF THE INVENTION

The present invention comprises phospholane compounds represented by thefollowing formula I ##STR1## wherein:

R is a lower alkyl, trifluoromethyl, phenyl, substituted phenyl,aralkyl, or ring substituted aralkyl; and

n is an integer from 1 to 12.

The present invention further comprises transition metal complexes ofcompounds of formula I.

A second aspect of the present invention further comprises phospholanecompounds represented by the following formula II ##STR2## wherein R andn are as defined above for formula I, and A is CCH₃, CH, N or P.

The present invention further comprises transition metal complexes ofcompounds of formula II.

A third aspect of the present invention comprises phospholane compoundsrepresented by the following formula III ##STR3## wherein:

R is an alkyl group of two to six carbon atoms, trifluoromethyl, phenyl,substituted phenyl, aralkyl, or ring substituted aralkyl.

A fourth aspect of the present invention comprises a process for thepreparation of compounds of formula I as described above wherein aphenyl substituted phospholane of formula III is reacted with lithiumand either 1) a dihalo compound of formula X-(CH₂)_(n) -X wherein X ishalogen, and n is an integer from 1 to 12, or 2) a compound of formulaR¹ O(CH₂)_(n) OR¹ wherein n is an integer from 1 to 12, and R¹ O or OR¹is methanesulfonate, trifluoromethanesulfonate or p-toluenesulfonate.

A fifth aspect of the present invention comprises a process for thepreparation of compounds of formula II wherein a compound of formula IIIas defined above is reacted with lithium and a trihalo compound offormula A[(CH₂)_(n) X]₃ wherein X is halogen, n is defined as above, andA is CCH₃, CH, N or P.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides chiral phospholane substituted alkanesuseful as ligands for transition metals in asymmetric catalysis. Theperalkylated nature of these compounds renders the phosphorus centerelectron rich. Transition metal complexes containing these ligandsdemonstrate a high level of enantioselective control and asymmetricinduction in the catalyzed hydrogenation of unsaturated substrates. Ithas been found that the close proximity of the chirality to the metalcenter of the complex results in an increase of the asymmetric inductionachieved.

This invention also provides an efficient stereospecific process for thepreparation of the chiral phospholanes. The availability of opticallyactive 1,4-diols with a high degree of enantiomeric purity permitspreparation of optically active phospholane compounds with a high degreeof enantiomeric purity.

The present invention comprises novel phospholane substituted alkanecompounds of formulae I and II ##STR4## wherein for each of formula Iand II:

R is a lower alkyl, trifluoromethyl, phenyl, substituted phenyl,aralkyl, or ring-substituted aralkyl; and

n is an integer from 1 to 12; and for formula II, A is CCH₃, CH, N or P.

The present invention further comprises transition metal complexes ofthese compounds.

Preferred are compounds of formulae I and II wherein R is a lower alkylof C₁ to C₆ alkyl and n is 1 to 3. Most preferred are those compounds offormula I and II wherein R is methyl and n is 1 to 3.

Examples of such compounds include, but are not limited to, 1,2-bis[(2R,5R)-2,5-dimethylphospholano]ethane; 1,3-bis[(2R,5R)-2,5-dimethylphospholano]propane; tris[((2S,5S)-2,5-dimethylphospholano)methyl]methane; tris[2-([2R,5R]-2,5-dimethylphospholano)ethyl]amine; or 1,1,1-tris[2-([2R,5R]-2,5-dimethylphospholano)ethyl]ethane.

The above phospholane compounds of formulae I and II can be complexedwith any of the transition metals of Groups 3 through 12 of the periodictable, plus the lanthanides and actinides. Due to the electron-richnature of the phospholane compounds they generally coordinate best withthe transition metals of Groups 4 through 10. Such complexes are formedby methods known in the art. Preferred transition metal complexes of thepresent invention are those comprising the above described preferredcompounds complexed with rhodium.

The phospholane compounds of formulae I and II of the present inventionare useful as transition metal ligands in asymmetric catalysis. The useof these ligands in transition metal catalysts results in a high levelof enantioselective and stereochemical control in the catalyzedhydrogenation of unsaturated substrates.

By a high level of enantioselectivity is meant a hydrogenation thatyields a product of greater than or equal to about 80%, preferably,greater than or equal to about 90% enantiomeric excess (abbreviated ee).

Enantiomeric excess is defined as the ratio (% R-% S)/(% R+% S), where %R is the percentage of R enantiomer and % S is the percentage of Senantiomer in a sample of optically active compound.

For the purpose of this application, by a "compound with a high degreeof enantiomeric purity", or a "compound of high enantiomeric purity" ismeant a compound that exhibits optical activity to the extent of greaterthan or equal to about 90%, preferably, greater than or equal to about95% enantiomeric excess (abbreviated ee).

A further aspect of the present invention comprises the phospholanecompounds of formula III ##STR5## wherein R is an alkyl group having 2to 6 carbon atoms, trifluoromethyl, phenyl, substituted phenyl, aralkyl,or ring substituted aralkyl.

Preferred compounds of formula III are those wherein R is an alkyl groupof 2 to 6 carbon atoms.

The phospholane compounds of formula III of the present invention areuseful as intermediates in the preparation of the compounds of formulaeI and II.

Another aspect of the present invention comprises processes for thepreparation of compounds of formulae I, II and III. The phospholanecompounds are prepared by processes of the present invention whichprovide high yields and high substrate stereo-selectivity. The processesare summarized in reaction Scheme I hereinafter. ##STR6##

The first step introduces the desired chirality and utilizes a Ru(BINAP)[Ru-(R)-(+) or (S)-(-)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl]catalyst as taught in Noyori et al., J. Amer. Chem. Soc., Vol. 110, p.629 (1988), which is herein incorporated by reference, for theasymmetric reduction of a β-keto ester to the corresponding β-hydroxyester. Hydrolysis with a strong base such as KOH provides the freecarboxylic acid, which is then subjected to electrochemicalKolbe-coupling to afford a chiral diol. In the Kolbe-coupling reaction aβ-hydroxy carboxylic acid of formula R¹ R² C(OH)CH₂ COOH, wherein R¹ andR² are each independently hydrogen, lower alkyl, phenyl, substitutedphenyl, aralkyl or ring-substituted aralkyl, or R¹ and R² are joinedtogether to form a 4-, 5-or 6-membered ring, is dissolved or suspendedin a lower alcohol solvent, together with a catalytic amount of acorresponding alkali metal alkoxide. Electrical current is then passedthrough the solution or suspensions and the chiral diol product isolatedby methods known in the art. The chiral diol is reacted with analkylsulfonyl chloride, preferably methanesulfonyl chloride, in thepresence of a tertiary amine such as triethylamine to form thebis(alkylsulfonate) derivative of the diol. Dilithium phenylphosphide isthen added to obtain the chiral 2,5 -disubstituted-1-phenylphospholaneof formula III.

The preparation of phospholane compounds of formulae I and II using thecompounds of formula III requires two additional steps. Treatment of aphenylphospholane of formula III with lithium with a clean metallicsurface results in selective cleavage of the phenyl group and yields amixture of 2,5-disubstituted lithium phosphide and phenyllithium. Thisreaction is conducted in tetrahydrofuran or an equivalent solvent. It isconducted at a temperature range of from about 0° C. to about 40° C.,preferably from about 20° C. to about 25° C. This reaction is conductedin the absence of oxygen and water under an inert atmosphere at apressure of about 1 atm. Preferably the inert atmosphere is argon.Agitation is required since it is a heterogenous reaction with lithiummetal. The overall reaction time can rabge from about 5 to about 30hours, and typically is from about 10 to about 20 hours.

The resulting mixture is then reacted directly with a compound offormula R¹ O(CH₂)_(n) OR¹ wherein OR¹ or R¹ O is methanesulfonate,trifluoromethanesulfonate, or p-toluenesulfonate, or with a dihaloalkane of formula X-(CH₂)_(n) -X wherein X is halogen, preferably chloroor bromo, to obtain the desired chiral chelating bis(phospholanes) offormula I. Reacting the mixture with a compound of formula A[(CH₂)_(n)X]₃ wherein X is halogen, preferably chloro or bromo; A is CCH₃, CH, Nor P; and n is 1 to 12; yields the desired tris(phospholanes) of formulaII. These reactions are conducted at a temperature range of from about-78° C. to about 40° C., preferably at from about 0° C. to about 25° C.,in tetrahydrofuran solvent. An inert atmosphere is employed, preferablyargon or nitrogen at about 1 atm. pressure. The reaction mixture isagitated. The overall reaction time for these reactons is from about 0.5to about 2 hours, typically from about 0.5 to about 1 hour. The desiredproduct is isolated using methods well known in the art such asdistillation, crystallization, evaporation of solvent, filtration,chromatography and the like.

The following examples illustrate the present invention but are notintended to limit it in any manner.

GENERAL PROCEDURES

All reactions and manipulations were performed in a nitrogen-filledVacuum Atmospheres Dri-Lab glovebox or using standard Schlenk (inertatmosphere) techniques. Benzene, toluene, diethyl ether (Et₂ O),tetrahydrofuran (THF), glyme, hexane, and pentane were distilled fromsodium benzo-phenone ketyl under nitrogen. Acetonitrile (CH₃ CH) andmethylene chloride (CH₂ Cl₂) were distilled from CaH₂. Methanol (MeOH)was distilled from Mg(OMe)₂.

Melting points were determined using a Mel-Temp apparatus in capillariessealed under nitrogen and were uncorrected. HPLC analyses were performedusing a Hewlett Packard Model HP 1090 LC interfaced to a HP 9000 Series300 computer workstation. Optical Rotations were obtained using a PerkinElmer Model Polarimeter. NMR spectra were obtained on Nicolet NT-360wide-bore (360 MHz ¹ H, 145 MHz ³¹ P), Nicolet NMC-300 wide-bore (300MHz ¹ H, 120.5 MHz ³¹ P, 75.5 Mz ¹³ C) and Nicolet QM-300 narrow-bore(300 MHz ¹ H) spectrometers. ¹³ C and ³¹ P NMR chemical shifts werepositive downfield (and negative upfield) from external Me₄ Si and 85%H₃ PO₄, respectively. IR spectra were recorded on a Nicolet 5DXB FT-IRspectrometer. Elemental analyses were performed by Oneida ResearchServices, Inc., Whitesboro, N.Y., or Schwarzkopf MicroanalyticalLaboratory, Inc., Woodside, N.Y.

The precursor chiral β-hydroxy esters used in the following examples ofdiol synthesis were prepared as described by Noyori et al., J. Amer.Chem. Soc., 109, 5856 (1987) which is herein incorporated by reference.The asymmetric reduction of β-keto esters to the β-hydroxy esters wasconducted using a ruthenium catalyst bearing the chiral phosphine ligandBINAP, (R)-(+) or (S)-(-)-2,2'-bis(diphenylphosphine)-1,1'-binaphthyl,(both enantiomers commercially available from Strem Chemicals, 7Mulliken Way, Dexter Industrial Park, P.O. Box 108, Newburyport, Mass.01950).

EXAMPLE 1

a) Preparation of chiral β-hydroxy acids. A mixture of methyl(3R)-3-hydroxypentanoate (290 g, 2.2 mol) in water (200 mL) and ethanol(200 mL) was cooled to 0° C. To this cold solution was added a solutionof KOH (185 g, 3.3 mol) in water (1 L). The reaction was then allowed tostir at 25° C. for 48 h. The resulting solution was concentrated to ca.500 mL and acidified (conc. HCl) until pH=1 was reached. Theprecipitated salts were filtered and the filtrate subjected tocontinuous liquid/liquid extraction with diethyl ether (1 L) for 24 h.The diethyl ether was removed on a rotovap to afford the productβ-hydroxy acid as a colorless oil (250 g, 97%). The crude product wassufficiently pure to use in the next step (Kolbe-coupling).

b) Preparation of (2R,5R)-2,5-hexanediol. A 100 mL reaction vessel wascharged with (3R)-3-hydroxybutyric acid (1.0 g, 9.6 mmol), methanol (30mL) and sodium methoxide (1.0 mL of a 0.5N solution in methanol, 0.05mmol), and then was cooled to 0° C. Using a Pt foil anode (5 cm²), a Ptscreen cathode (5 cm²), and a 50 V/40 amp power supply, a constantcurrent (current density 0.25 A/cm²) was applied until 1388 coulombs(1.5 F/mol) were passed. The reaction and gas evolution (H₂ and CO₂)proceeded normally until ca. 1.0 F/mol current were passed, after whichthe resistance was observed to increase. The colorless solution wasconcentrated on a rotovap. Chromatography on SiO₂ (70% ethylacetate/hexane) afforded the product as a colorless crystalline solid(0.36 g, 64%). mp 53°-54° C.; [α] ²⁵ D=-37.6° (c 1, CHCl₃); ¹ H NMR (CD₂Cl₂) δ 1.15 (d, J_(HH) =6.2 Hz, 6H CH₃), 1.50 (m, 4H, CH₂), 2.95 (br,2H, OH), 3.75 (m, 2H, CH); ¹³ C NMR (CD₂ Cl₂) δ 23.6, 35.9, 68.1.

c) Preparation of (2R,5R)-2,5-hexanediol bis(methanesulfonate). To asolution of (2R,5R)-2,5-hexanediol (8.9 g, 0.075 mol) in CH₂ Cl₂ (200mL) was added triethylamine (26.2 mL, 0.188 mol). The solution wascooled to 0° C., and methanesulfonyl chloride (12.82 mL, 0.166 mol) inCH₂ Cl₂ (30 mL) was added dropwise over 30 min. Upon complete addition,the mixture containing precipitate salts was allowed to stir at 0° C.for 30 min, and then at 25° C. for 30 min. The mixture was then pouredinto 1N HCl (250 mL) at 0° C. After shaking, the layers were separatedand the aqueous layer was extracted with CH₂ Cl₂ (2×50 mL). The combinedorganic layers were washed successively with 1N HCl (50 mL), saturatedNaHCO₃, and brine. After drying (MgSO₄), the solution was concentratedon a rotovap to a pale yellow oil (18.2 g, 88%). The crude product thusobtained was sufficiently pure to be used in further reactions. ¹ H NMR(CDCl₃) δ 1.41 (d, J_(HH) =6.3 Hz, 6H, CH₃), 1.78 (m, 4H, CH₂), 3.0 (s,6H, CH₃), 4.85 (m, 2H, CH).

d) Preparation of (2R,5R)-2,5-dimethyl-1-phenylphospholane. To a slurryof Li₂ PPh-THF (20.3 g, 0.105 mol) in THF (300 mL) at -78° C. was addeddropwise a solution of (2S,5S)-2,5-hexanediol bis(methanesulfonate)(26.0 g, 0.095 mol) in THF (50 mL). Upon complete addition, the orangemixture was allowed to stir at -78° C. for 1 h. The reaction was thenslowly warmed to 25° C. and stirring was continued for 16 h. Theresulting pale yellow mixture was filtered through a coarse frit, andconcentrated to a semi-solid. Extraction with pentane (100 mL) andfiltration, followed by concentration in vacuo yields a pale yellow oil.Distillation afforded the product as a colorless oil (13.9 g, 76%): bp61°-64° C. (0.2 torr); [α]²⁵ D=-49.0°±2° (c 1, hexane); ¹ H NMR (C₆ D₆ )δ 0.70 (dd, J_(HH) =7.2 Hz, J_(PH) =10.6 Hz, 3H, CH₃), 1.1-1.3 (m, 2H,CH₂), 1.20 (dd, J_(HH) =7.2 Hz, J_(PH) =18.8 Hz, 3H, CH₃), 1.65 (m, 1H,CH), 2.0 (m, 2H, CH₂), 2.45 (m, 1H, CH); ³¹ P NMR (C₆ D₆) δ 10.0; ¹³ CNMR (C₆ D₆) δ 15.43 (CH₃), 21.23 (d, J_(PC) =34.2 Hz, CH₃), 32.25 (d,J_(PC) =10.0 Hz, CH), 35.62 (d, J_(PC) =13.1 Hz, CH), 37.17 (CH₂), 37.24(d, J_(PC) =3.6 Hz, CH₂), 128.11, 128.30, 134.51 (d, J_(PC) =19.0 Hz,ortho), 137.67 (d, J_(PC) =28.1 Hz, ipso Ph); HRMS (El, direct insert):m/z 192.1068 (M+, exact mass calcd for C₁₂ H₁₇ P: 192.1068), 177.0839(M-CH₃), 150.0559 (M-C₃ H₆), 135.0367 (M-C₄ H₉), 108.0127 (C₆ H₅ Pfragment).

e) (2S,5S)-2,5-dimethyl-1-phenylphospholane [α]²⁵ D=+51.6±2° (c 1,hexane). Other spectroscopic properties were identical to Example 1 d).

f) Preparation of 1,2-Bis((2R,5R)-2,5-dimethylphospholane)ethane. Tophospholane of Example 1 d) (6.0 g, 0.031 mol) in THF (200 mL) at 25° C.under Ar was added clean Li ribbon (0.54 g, 0.078 mol), and the reactionwas allowed to stir for 10 h. To the resulting brown/green mixture wasadded dropwise a solution of ethylene glycol di-p-tosylate (6.90 g,0.018 mol) in THF (100 mL). After stirring for 1 h, the mixture wasfiltered (coarse frit) and MeOH (2 mL) was added to the filtrate whichturned pale yellow. The reaction was allowed to stir for 30 min and thenfiltered. The filtrate was concentrated to dryness in vacuo, and theresulting solids were extracted with pentane (200 mL) and filtered. Thepentane filtrate was concentrated to a yellow oil which was distilled toafford the product as a colorless oil (2.10 g, 52%): bp 64°-67° C. (0.06torr); [ α]²⁵ D=+222±6° (c 1, hexane); ¹ H NMR (C₆ D₆) δ 0.98 (dd,J_(HH) =7.2 Hz, J_(PH) =9.1 Hz, 3H, CH₃), 1.0-1.35 (m, 5H, CH₂), 1.22(dd, J_(HH) =7.2 Hz, J_(PH) =17.3 Hz, 3H, CH₃), 1.55 (m, 2H, CH, CH₂),1.70 (m, 5H, CH, CH₂), 1.90 (m, 4H, CH, CH₂); ³¹ P NMR (C₆ D₆) δ 3.2; ¹³C NMR (C₆ D₆) δ 14.6 (CH₃), 20.71 (d, J_(PC) =6.0 Hz, CH₃), 21.48 (dd,J_(PC) =15.5 Hz, bridge CH₂), 34.44 (dd, J_(PC) =5.8, 5.9 Hz, ring CH),37.02 (ring CH₂), 37.42 (ring CH₂), 38.32 (dd, J_(PC) =5.5 Hz, ring CH);HRMS (El, direct insert): m/z 258.1670 (M+, exact mass calcd for C₁₄ H₂₈P₂ : 258.1667), 230.1344 (M-C₂ H₄), 175.0785 (M-C₆ H₁₁), 144.1072 (M-C₆H₁₁ P), 116.0748 (M-C₈ H₁₅ P).

g) Optical Purity of Phosphines. The phosphines of Example 1 d), e) andf) were ascertained to be optically pure (within the limits ofdetection) by reacting each with(R)-[dimethyl-(α-methylbenzyl)aminato-C,N]palladium (II) chloride dimerand monitoring the ³¹ P NMR spectrum. Comparisons were made with thespectrum of the opposite phosphine enantiomer.

EXAMPLE 2

Preparation of 1,3-Bis((2R,5R)-2,5-dimethylphospholano)propane. Tophospholane of Example 1 d) (6.0 g, 0.031 mol) in THF (200 mL) at 25° C.under Ar was added clean Li ribbon (0.54 g, 0.078 mol), and the reactionwas allowed to stir for 10 h. To the resulting brown/green mixture wasadded dropwise a solution of 1,3-dichloropropane (2.11 g, 0.018 mol) inTHF (25 mL). The reaction decolorized towards the end of the addition,and after stirring for 30 min, MeOH (2 mL) was added. This mixture wasallowed to stir 10 min, then was filtered, and the filtrate concentratedin vacuo. The resulting oil was extracted with pentane (125 mL),filtered, and the pentane layer was concentrated to a yellow oil.Distillation afforded the product as a colorless oil (3.2 g, 75%): bp98°-101° C. (0.08 torr); [α]²⁵ D=+279±6 (c 1, hexane); ¹ H NMR (C₆ D₆) δ1.0 (dd, J_(HH) =7.1 Hz, J_(PH) =9.6 Hz, 3H, CH₃), 1.05 (m, 2H, CH₂),1.20 (dd, J_(HH) =7.1 Hz, J_(PH) =17.5 Hz, 3H, CH₃), 1.20 (m, 2H, CH₂),1.40 (m, 2H, CH₂), 1.55 (m, 4H, CH₂), 1.70 (m, 4H, CH, CH₂), 1.90 (m,4H, CH, CH₂); ³¹ P NMR (C₆ D₆) δ -2.85; ¹³ C NMR (C₆ D₆) δ 14.6 (CH₃),21.45 (d, J_(PC) =30.8 Hz, CH₃), 24.34 (t, J_(PC) =18.9 Hz, bridgecentral CH₂), 25.70 (dd, J_(PC) =11.3, 22.3 Hz, bridge CH₂), 34.05 (d,J_(PC) =12.1 Hz, ring CH), 37.10 (d, J_(PC) =3.6 Hz, ring CH₂), 37.51(ring CH₂), 38.30 (d, J_(PC) =11.5 Hz, ring CH); HRMS (El, directinsert): m/z 272.1816 (M+ exact mass calcd for C₁₅ H₃₀ P₂ : 272.1823),229.1283 (M-C₃ H₇), 188.0831 (M-C₆ H₁₂), 157.1139 (M-C₆ H₁₂ P), 130.0900(M-C₈ H₁₅ P), 116.0742 (C₆ H₁₃ P fragment).

Optical Purity. The phosphine of Example 2 was ascertained to beoptically pure (within the limits of detection) by reacting it with(R)-[dimethyl-(α-methylbenzyl)-aminato-C,N]palladium (II) chloride dimerand monitoring the ³¹ P NMR spectrum. Comparisons were made with thespectrum of the opposite phosphine enantiomer.

EXAMPLE 3

a) Rhodium complex[(COD)Rh(1,3-bis((2R,5R)-2,5-dimethylphospholano)propane)]⁺ PF₆ ⁻. To amixture of [(COD)RhCl]₂ (0.44 g, 0.89 mmol, COD=1,5-cyclooctadiene) andNaPF₆ (0.40 g, 2.4 mmol) in THF (20 mL) at 25° C. was added dropwise asolution of 1,3-bis((2R,5R)-2,5-dimethylphospholano)propane (0.50 g, 1.8mmol) in THF (5 mL). The solution turned orange from yellow upon thephosphine addition. The reaction was allowed to stir for 30 min, andthen was concentrated to a volume of ca. 5 mL. The slow addition of Et₂O (30 mL) to the solution produced an orange precipitate which wasfiltered, washed with Et₂ O, and briefly dried. The solids weredissolved in CH₂ Cl₂ (5 mL), filtered, and Et₂ O (30 mL) was addedslowly to the orange filtrate to provide the product as an orangemicrocrystalline solid (0.86 g, 75%); ¹ H NMR (CD₂ Cl₂) δ 1.15 (dd,J_(HH) =6.9 Hz, J_(PH) =14.8 Hz, 6H, CH₃), 1.50 (dd, J_(HH) =7.2 Hz,J_(PH) =18.7 Hz, 6H, CH₃), 1.3-1.6 (m, 6H, CH₂), 1.80 (m, 2H, CH, CH₂),2.10 (m, 4H, CH, CH₂), 2.20-2.60 (m, 12H, CH₂, CH), 4.80 (m (br), 2H,COD-CH), 5.15 (m (br), 2H, COD-CH); ³¹ P NMR (CD₂ Cl₂) δ 27.7 (d,J_(RhP) =139.6 Hz), -145 (sept., PF₆); Anal. Calcd for C₂₃ H₄₂ F₆ P₃ Rh:C, 43.96; H, 6.74. Found: C, 44.19; H, 6.43.

b) Rhodium complex [(COD)Rh((2R, 5R)-2,5-dimethyl-1-phenylphospholane)₂]⁺ SbF₆ ⁻. This complex was prepared in a manner analogous to that ofExample 3 a). ¹ H NMR (CD₂ Cl₂) δ 0.70 (dd, J_(HH) =6.9 Hz, J_(PH) =13.8Hz, 6H, CH₃), 1.00 (m, 2H, CH₂), 1.40 (m, 2H, CH₂), 1.62 (dd, J_(HH)=7.2 Hz, J_(PH) =18.6 Hz, 6H, CH₃), 1.90 (m, 2H, CH₂, CH), 2.20 (m, 6H,CH₂, CH), 2.40 (M, 8H, COD-CH₂), 4.90 (br, 2H, COD-CH), 5.34 (br, 2H,COD-CH), 7.0 (m, 4H, Ph), 7.30 (m, 4H, Ph), 7.40 (m, 2H, Ph); ³¹ P NMR(CD₂ Cl₂) δ 43.8 (d, J_(RhP) =143.4 Hz). Anal. calcd. for C₃₂ H₄₆ P₂ F₆SbRh: C, 46.23; H, 5.58; P, 7.45. Found: C, 46.26; H. 5.47; P, 7.43.

X-ray Crystallographic Analysis. Crystal data for C₃₂ H₄₆ F₆ P₂ RhSb:monoclinic, P21 (No. 4), a=12.184(a) Å, b=12.734(2) Å, c=10.771(1) Å,β=96.83(1)°, T=-100° C, V=1659.3 Å³, Mo Kα radiation, μ_(calcd) =14.58cm⁻¹, d_(calcd) =1.664 gcm⁻³, Z=2, FW=831.33.

Suitable crystals of the rhodium complex were obtained by slow vapordiffusion of Et₂ O into a CH₂ Cl₂ solution at 25° C. An orange needle ofdimensions 0.16×0.32×0.38 mm was mounted in a nitrogen-filledthin-walled glass capillary, and data was collected on a Syntex R3diffractometer at -100° C. The unit cell dimensions were determined byleast squares refinement of 49 reflections. The crystal stability wasmonitored throughout the data collection by measuring the intensity ofthree standard reflections every 180 data points. The data were adjustedfor a 2% decrease in intensity over the course of data acquisition.Lorentzian, polarization and absorption (azimuthal) corrections wereapplied, due to the relatively large absorption coefficient μ(Mo)-14.58cm⁻¹.

The structure was solved using direct methods (SHELXS). All hydrogenatoms were determined from difference Fourier maps and idealized(C-H=0.95 Å). Anisotropic refinement was carried out by full-matrixleast squares on F.

Neutral atom scattering factors and anomalous scattering terms for P,Rh, and Sb were obtained from the International Tables for X-rayCrystallography, Vol. IV, herein incorporated by reference. Non-hydrogenatoms were refined anisotropically, and the hydrogens were refinedisotropically for a total of 378 parameters. The refinement coverged atR=0.035, R_(w) =0.041, and EOF=1.61 for 6845 unique reflections with1>3.0σ(1). Fractional coordinates and isotropic thermal parameters forall non-H atoms were provided in Table S-1, while anisotropic thermalparameters were given in Table S-2. A complete listing of bond lengthsand angles were also supplied.

The structure consisted of discrete molecules in which the usual squareplanar geometry of Rh(I) was somewhat distorted. The molecule had C₂symmetry, but the 1,5-cyclooctadiene ring was rotated out of the P-Rh-Pplane by 17.1 degrees. This distortion was the result of interactionswith the methyl groups of the phosphine ligands. The Rh-C distances alsowere disparate with C1 and C5 being closer than C2 and C6. The ratherlarge thermal motion of the phenyl rings and the fluorine atoms wereself-evident and limited the quality of the structure. Attempts torefine the hydrogen atoms were unsatisfactory and these atoms wereidealized and fixed with isotropic thermal parameters one higher thantheir associated carbon atoms. A full hemisphere of data was used in therefinement of the structure; the enantiomorphic structure refined tohigher values R=0.039 and R_(w) =0.048.

c) Rhodium complex [(COD)Rh-Bis((2R,5R)-2,5-dimethylphospholano)ethane]⁺ SbF₆ ⁻. This complex was preparedin a manner analogous to that of Example 3 a). ¹ H NMR (CD₂ Cl₂) δ 1.20(dd, J_(HH) =6.9 Hz, J_(PH) =14.4 Hz, 6H, CH₃), 1.40 (dd, J_(HH) =7.1Hz, J_(PH) =17.7 Hz, 6H, CH₃), 1.3-1.6 (m, 6H, CH₂), 1.95 (m, 2H, CH,CH₂), 2.10-2.60 (m, 10H, CH₂, CH), 4.95 (br, 2H, COD-CH), 5.40 (br, 2H,COD-CH); ³¹ P NMR (CD₂ Cl₂) δ 76.7 (d, J_(RhP) =146.3 Hz). Calcd. forC₂₂ H₄₀ F₆ P₂ SbRh: C, 37.47; H, 5.72. Found: C, 37.64; H, 5.37.

X-ray Crystallographic Analysis. Suitable crystals of the rhodiumcomplex were obtained by slow crystallization from a CH₂ Cl₂ /hexane(2/1) solution at 25° C. An orange needle of dimensions 0.10×0.12×0.71mm was mounted in a nitrogen-filled thin-walled glass capillary, anddata was collected on a Syntex R3 diffractometer at -100° C. The unitcell dimensions were determined by least squares refinement of 49reflections. The crystal stability was monitored throughout the datacollection by measuring the intensity of three standard reflectionsevery 182 data points. The data were adjusted for a 4% decrease inintensity over the course of data acquisition. Lorentzian, polarizationand absorption (azimuthal) corrections were applied, due to therelatively large absorption coefficient μ (Mo)=17.72 cm⁻¹.

The structure was solved using direct methods (SHELXS). All hydrogenatoms were determined from difference Fourier maps and idealized(C-H-0.95 Å). Anisotropic refinement was carried out by full-matrixleast squares on F. Neutral atom scattering factors and anomalousscattering terms for P, Rh, and Sb were obtained from the InternationalTables for X-ray Crystallography, Vol. IV, herein incorporated byreference. Non-hydrogen atoms were refined anisotropically, and thehydrogens were refined isotropically for a total of 289 parameters. Therefinement converged at R=0.038, R_(w) =0.036, and EOF=1.07. Fractionalcoordinates and isotropic thermal parameters for all non-H atoms wereprovided in Table S-1, while anisotropic thermal parameters were givenin Table S-2. A complete listing of bond lengths and angles were alsosupplied.

Like the Rh complex of Example 3 a), this structure consisted ofdiscrete molecules in which the usual square planar geometry wasdistorted to an even greater extent. The complex had essentially C₂symmetry with the 1,5-cyclooctadiene ligand rotated well out of theP-Rh-P plane by 24.3 degrees.

EXAMPLE 4

Hydrogenation Procedure. In a dry box, a 100 mL Fisher-Porter tube wascharged with substrate (1.26 mmol), dry degassed MeOH or THF (20 mL),and the catalyst of Example 3 a), b) or c) (0.2 mol %). After twofreeze-pump-thaw cycles, the tube was pressurized to an initial pressureof 10 psig with H₂ (Matheson, 99.998%). The reactions were allowed tostir at 25° C. for 3-12 h. Hydrogen uptake was monitored and completereaction was indicated by GC and NMR analyses. Reactions were worked-upas previously described. Enantiomeric excesses were determined by HPLC(methyl acetamidophenylalanine, Chiralcel OB, 5% IPA/Hexane) or shiftreagent (dimethyl methylsuccinate, (+)-Eu(hfc)₃) analyses. The resultingdata is listed in Table I.

                  TABLE I                                                         ______________________________________                                        Substrate         Enantiomeric Excess                                         ______________________________________                                        Methyl acetamidocinnamate                                                                       85%                                                         Dimethyl itaconate                                                                              91%                                                         ______________________________________                                    

EXAMPLE 5

Preparation of Tris[((2S, 5S)-2,5-dimethylphospholano)methyl]methane. To(2S, 5S)-2,5-dimethyl-1-phenylphospholane (6.07 g, 0.032 mol) in THF(200 mL) at 25° C. under Ar was added clean Li ribbon (0.55 g, 0.079mmol), and the reaction was allowed to stir for 15 h. To the resultingbrown-orange mixture was added dropwise a solution of1,3-dichloro-2-(chloromethyl)propane (1.70 g, 10.5 mmol) in THF (15 mL)at 25° C. The reaction remained brown throughout the addition, and afterstirring for 30 min, MeOH (3 mL) was added. The resulting colorlessmixture was allowed to stir 15 min, then was filtered through a celitepad, and the filtrate concentrated in vacuo. The resulting solids wereextracted with pentane (125 mL), filtered, and the pentane layer wasconcentrated to ca. 15 mL. Rapid filtration afforded the product as acolorless crystalline solid (1.0 g). The filtrate was then concentratedto a pale yellow solid which was dissolved in a minimum amount of Et₂ O(3 mL). To this solution was added MeOH (15 mL) and the mixture wascooled to -20° C. for 12 h. The resulting white crystals were filtered,washed with cold MeOH and dried in vacuo (1.65 g). Combined yield 2.65 g(63%): [α]²⁵ D=-329°±6° (c 1, hexane); ¹ H NMR (C₆ D₆) δ 1.0-1.2 (m, 3H,CH, CH₂), 1.07 (dd, J_(HH) =7.2 Hz, J_(PH) =9.8 Hz, 9H, CH₃), 1.29 (dd,J_(HH) =7.0 Hz, J_(PH) =17.6 Hz, 9H, CH₃), 1.40 (m, 3H, CH, CH₂), 1.60(m, 3H, CH₂), 1.80 (m, 3H, CH, CH₂), 1.9-2.2 (m, 13H, CH, CH₂); ³¹ P NMR(C₆ D₆) δ -8.0; ¹³ C NMR (C₆ D₆) δ 14.89 (CH₃), 21.51 (d, J_(PC) =30.7Hz, CH₃), 31.85 (dt, J_(PC) =8.3, 22.1 Hz, bridge P-CH₂), 32.67 (q,J_(PC) =14.9 Hz, bridge CH), 34.12 (d, J_(PC) =11.6 Hz, ring CH), 37.30(d, J_(PC) =3.8 Hz, ring CH₂), 37.47 (ring CH₂), 38.49 (d, J_(PC) =11.3Hz, ring CH); HRMS (E1, direct insert): m/z 400.2583 (M+ exact masscalcd for C₂₂ H₄₃ P₃ : 400.2578), 357.2021 (M-C₃ H₇), 315.1557 (M-C₆H₁₃), 285.1896 (M-C₆ H₁₂ P), 273.1104 (M-C₉ H₁₉), 232.0678 (M-C₁₂ H₂₄),201.0955 (M-C₁₂ H₂₄ P).

EXAMPLE 6

Preparation of Tris(2-((2R, 5R)-2,5-dimethylphospholano)ethyl)amine. To(2R, 5R)-2,5-dimethyl-1-phenylphospholane (3.0 g, 15.6 mmol) in THF (100mL) at 25° C. under Ar was added clean Li ribbon (0.27 g, 39.0 mmol),and the reaction was allowed to stir for 15 h. To the resultingbrown/orange mixture was added dropwise a solution oftris(2-chloroethyl)amine (1.06 g, 5.2 mmol) in THF (15 mL) at 25° C. Thereaction remained brown throughout the addition, and after stirring for30 min, MeOH (3 mL) was added. The resulting colorless mixture wasallowed to stir 15 min, then was filtered through a celite pad, and thefiltrate concentrated in vacuo. The resulting solids were extracted withpentane (125 mL), filtered, and the pentane layer was concentrated toca. 15 mL. Rapid filtration afforded the product as a colorlesscrystalline solid (0.6 g). The filtrate was then concentrated to a paleyellow solid which was dissolved in a minimum amount of Et₂ O (3 mL). Tothis solution was added MeOH (10 mL) and the mixture was cooled to -20°C. for 12 h. The resulting white crystals were filtered, washed withcold MeOH and dried in vacuo (1.13 g). Combined yield 1.73 g (75%):[α]²⁵ D=+167±2(c 1, hexane); ¹ H NMR (C₆ D₆) δ 1.0-1.2 (m, 3H, CH, CH₂),1.11 (dd, J_(HH) =7.2 Hz, J_(PH) =9.8 Hz, 9H, CH₃), 1.32 (dd, J_(HH)=7.0 Hz, J_(PH) =17.7 Hz, 9H, CH₃), 1.30-1.45 (m, 3H, CH, CH₂), 1.55 (m,3H, CH₂), 1.70-2.15 (m, 15H, CH, CH₂), 2.80 (m, 6H, NCH₂); ³¹ P NMR(C.sub. 6 D₆) δ -3.4.

EXAMPLE 7

Preparation of 1,1,1-Tris(2-((2R,5R)-2,5-dimethylphospholano)ethyl)ethane. To (2R,5R)-2,5-dimethyl-1-phenylphospholane (0.53 g, 2.76 mmol) in THF (10 mL)at 25° C. under Ar was added clean Li ribbon (0.048 g, 6.9 mmol), andthe reaction was allowed to stir for 15 h. To the resulting brown/orangemixture was added dropwise a solution of 1,1,1-tris(2-chloroethyl)ethane(0.2 g, 0.92 mmol) in THF (5 mL) at 25° C. The reaction remained brownthroughout the addition, and after stirring for 30 min, MeOH (1 mL) wasadded. The resulting colorless mixture was allowed to stir 15 min, thenwas filtered through a celite pad, and the filtrate concentrated invacuo. The resulting solids/oil were extracted with pentane (50 mL),filtered, and the pentane layer was concentrated to yield the product asa colorless, viscous oil (0.257 g, 61%): ¹ H NMR (C₆ D₆) δ 0.84 (s, 3H,CH₃), 1.11 (dd, J_(HH) =6.9 Hz, J_(PH) =9.8 Hz, 9H, CH₃), 1.20 (dd,J_(HH) =7.2 Hz, J_(PH) =17.6 Hz, 9H, CH₃), 1.00-1.50 (m, 18H, CH, CH₂),1.80 (m, 3H, CH₂), 1.90-2.15 (m, 9H, CH, CH₂); ³¹ P NMR (C₆ D₆) δ 0.3;HRMS (El, direct insert): m/z 456.3170 (M⁺ exact mass calcd for C₂₆ H₅₁P₃ : 456.3204), 371.2206 (M-C₆ H₁₃), 341.2645 (M-C₆ H₁₂ P), 257.1612(M-C₁₂ H₂₄ P).

What is claimed is:
 1. A compound represented by the following formulaIII: ##STR7## wherein R is an alkyl group of one to six carbon atoms,trifluoromethyl, or phenyl.
 2. A compound of claim 1 having a highdegree of enantiomeric purity.
 3. The transition metal complex which is[(COD)Rh((2R,5R)-2,5-dimethyl-1-phenylphospholane)2]-⁺ SbF₆ ⁻.